Cancer is a significant health problem throughout the world. Significant resources have been devoted to seeking cures for cancer resulting in important advances in the detection and treatment of cancer. However, there is significant need for new therapeutic agents having increased efficacy and reduced side effects. Current therapies, many of which involve a combination of chemotherapy or surgery and radiation, are inadequate for many patients. One of the early cancer chemotherapy drugs was the alkylating agent cyclophosphamide (Endoxan®), which is an oxazaphosphorin pro-drug activated preferentially in a tumor. The target of alkylating agents like cyclophosphamide is DNA and the concept, that cancer cells with uncontrolled proliferation and a high mitotic index are killed preferentially, has been confirmed. Historically, cancers have been linked to genetic changes caused by chromosomal mutations within the DNA. Mutations, hereditary or acquired, can lead to a loss of gene expression critical for maintaining a healthy state.
Many standard cancer chemotherapeutic drugs kill cancer cells upon induction of programmed cell death (“apoptosis”) by targeting basic cellular processes and molecules. These basic cellular processes and molecules include RNA/DNA (alkylating and carbamylating agents, platin analogs and topoisomerase inhibitors), metabolism (drugs of this class are named anti-metabolites and examples are folic acid, purine and pyrimidine antagonists) as well as the mitotic spindle apparatus with α,β-tubulin heterodimers as the essential component (drugs are categorized into stabilizing and destabilizing tubulin inhibitors; examples are Taxol/Paclitaxel®, Docetaxel/Taxotere® and vinca alkaloids). Yet agents such as these are insufficient treatments, as evidenced by the following statistics for breast, prostrate, and lung cancer, for example.
Prostate cancer is the most common form of cancer among males, with an estimated incidence of 30% in men over the age of 50. Moreover, clinical evidence indicates that human prostate cancer has the propensity to metastasize to bone, and the disease appears to progress inevitably from androgen dependent to androgen refractory status, leading to increased patient mortality. This prevalent disease is one of the leading causes of cancer death among men in the United States.
The incidence of breast cancer, a leading cause of death in women, has been gradually increasing in the United States over the last thirty years. Its cumulative risk is relatively high; certain reports indicate that approximately one in eight women are expected to develop some type of breast cancer by age 85 in the United States. In fact, breast cancer is one of the most common cancers in women and still remains a leading cause of cancer death in the United States.
Lung cancer is a leading cause of cancer-related death, and non-small cell lung cancer (NSCLC) accounts for about 80% of these cases. Attempts to use serum protein markers for the early diagnosis of lung cancer have not yielded satisfactory results for routine screening, and newly developed early diagnostic methods using serum DNA as a diagnostic marker await further validation. Moreover, current therapeutic measures are frequently unable to lower the mortality rate of late-stage lung cancer patients. Of the current therapeutic measures, surgical resection is the best cure currently available for early-stage patients. However, a large portion of early-stage patients, defined by the current staging system and available imaging modalities, still develop distant metastases even after surgical removal of the tumor mass.
In view of the foregoing, the need exists for more effective compositions and methods for treating cancers of all types, including prostrate, breast, and lung cancers, as well as colon cancer, ovarian cancer, leukemia, renal cancer, melanoma and central nervous system cancer. The present invention addresses this need and has other related advantages.